11-60069719-C-T

Variant names:

• chr11-60069719-C-T
• rs2298585
• NM_006138.5:c.615+44C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006138.5(MS4A3):​c.615+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00936 in 1,435,424 control chromosomes in the GnomAD database, including 569 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (445 hom.)
• Consequence: MS4A3 NM_006138.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 15 publications found

Genes affected

MS4A3 (HGNC:7317): (membrane spanning 4-domains A3) This gene encodes a member of the membrane-spanning 4A gene family. Members of this protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This family member likely plays a role in signal transduction and may function as a subunit associated with receptor complexes. The gene encoding this protein is localized to 11q12, among a cluster of related family members. Alternative splicing may result in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A3	NM_006138.5	c.615+44C>T		intron_variant	Intron 6 of 6	ENST00000278865.8	NP_006129.4
MS4A3	NM_001031809.2	c.477+44C>T		intron_variant	Intron 5 of 5		NP_001026979.1
MS4A3	NM_001031666.2	c.246+44C>T		intron_variant	Intron 4 of 4		NP_001026836.1
MS4A3	XM_011545363.4	c.435+44C>T		intron_variant	Intron 5 of 5		XP_011543665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A3	ENST00000278865.8	c.615+44C>T		intron_variant	Intron 6 of 6	1	NM_006138.5	ENSP00000278865.3

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3603 AN: 152126 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0159 AC: 3984 AN: 249952 AF XY: 0.0142

Gnomad AFR exome AF: 0.0651

Gnomad AMR exome AF: 0.00453

Gnomad ASJ exome AF: 0.000697

Gnomad EAS exome AF: 0.119

Gnomad FIN exome AF: 0.000189

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.00766 AC: 9827 AN: 1283180 Hom.: 445 Cov.: 18 AF XY: 0.00756 AC XY: 4894 AN XY: 647204

African (AFR) AF: 0.0657 AC: 1953 AN: 29738

American (AMR) AF: 0.00480 AC: 213 AN: 44356

Ashkenazi Jewish (ASJ) AF: 0.000883 AC: 22 AN: 24926

East Asian (EAS) AF: 0.130 AC: 5056 AN: 38746

South Asian (SAS) AF: 0.0109 AC: 898 AN: 82068

European-Finnish (FIN) AF: 0.000516 AC: 27 AN: 52320

Middle Eastern (MID) AF: 0.00646 AC: 35 AN: 5422

European-Non Finnish (NFE) AF: 0.000936 AC: 890 AN: 951100

Other (OTH) AF: 0.0134 AC: 733 AN: 54504

GnomAD4 genome AF: 0.0237 AC: 3612 AN: 152244 Hom.: 124 Cov.: 32 AF XY: 0.0242 AC XY: 1800 AN XY: 74456

African (AFR) AF: 0.0640 AC: 2658 AN: 41518

American (AMR) AF: 0.00968 AC: 148 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.121 AC: 626 AN: 5174

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000911 AC: 62 AN: 68022

Other (OTH) AF: 0.0147 AC: 31 AN: 2116

Alfa AF: 0.00945 Hom.: 180

Bravo AF: 0.0266

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2298585; hg19: chr11-59837192;